Lichen planus is associated with other autoimmune conditions: A retrospective population-level study
Authors: Alexa Kassels, Ashley N. Elsensohn, Christina N. Kraus
Journal: Journal of the American Academy of Dermatology (2023)

To the Editor: Lichen planus (LP) is a T-cell mediated chronic inflammatory skin disease that affects mucocutaneous surfaces. LP has been associated with autoimmune conditions like alopecia areata, autoimmune thyroiditis, celiac disease, dermatomyositis (DM), type 1 diabetes mellitus, Sjogren's syndrome, and systemic lupus erythematosus.1Aghamajidi A. Raoufi E. Parsamanesh G. et al.The attentive focus on T cell-mediated autoimmune pathogenesis of psoriasis, lichen planus and vitiligo.Scand J Immunol. 2020; 93e13000Crossref PubMed Scopus (17) Google Scholar, 2De Porras-Carrique T. Ramos-García P. Aguilar-Diosdado M. Warnakulasuriya S. González-Moles M.Á. Autoimmune disorders in oral lichen planus: a systematic review and meta-analysis.Oral Dis. 2022; 29: 1382-1394Crossref PubMed Scopus (9) Google Scholar, 3Chung P.-I. Hwang C.-Y. Chen Y.-J. et al.Autoimmune comorbid diseases associated with Lichen planus: a nationwide case-control study.J Eur Acad Dermatol Venereol. 2014; 29: 1570-1575https://doi.org/10.1111/jdv.12939Crossref PubMed Scopus (23) Google Scholar, 4Cooper S.M. Ali I. Baldo M. Wojnarowska F. The Association of Lichen sclerosus and erosive lichen planus of the vulva with autoimmune disease.Arch Dermatol. 2008; 144Crossref Scopus (172) Google Scholar We performed a population-level retrospective study using extensive data from numerous health care organizations throughout the US to explore whether additional autoimmune conditions are associated with LP and confirm previously found associations. We utilized TriNetX, a global health research network, to retrospectively generate a patient cohort from the US Collaborative Network. Our study included data between June 2003 and 2023 of over 95 million patients from 57 US health care organizations. International Classification of Diseases-10 (ICD-10) code L43 was used for LP and L20.9 was used for atopic dermatitis (AD). AD was used as the control cohort. Patients with LP were excluded from the control cohort. Diagnoses prior to ICD-10 codes were mapped by TriNetX using General Equivalence Mappings. The cohorts were 1:1 propensity score matched by age, sex, and race/ethnicity. We then utilized ICD-10 codes to identify patients who were diagnosed with autoimmune conditions following a diagnosis of LP. Odds ratios and 95% confidence intervals were utilized to identify associations between LP and other conditions. We identified 77,060 LP patients and an equal number of matched controls (Table I). Patients with LP had increased odds of: alopecia areata, autoimmune thyroiditis, DM, discoid lupus erythematosus, lichen sclerosus (LS), morphea, other local lupus erythematosus, primary biliary cirrhosis, Sjogren's syndrome, subacute cutaneous lupus erythematosus, systemic lupus erythematosus, systemic sclerosis, and vitiligo. Patients with LP had decreased odds of inflammatory arthritis, rheumatoid arthritis, multiple sclerosis, psoriasis, type 1 diabetes mellitus, and vitamin D deficiency. We found no association between LP and celiac disease, Crohn's disease, myasthenia gravis, psoriatic arthritis, reactive arthritis, or ulcerative colitis (Table II).Table IPatient demographics for lichen planus and control cohorts after propensity score matchingCharacteristicNo (%)Lichen planus (n = 77,060)No (%)Control (n = 77,060)Age, mean (SD)63.8 (16.8)63.8 (16.8)Female52,794 (68.510)52,763 (68.470)Male24,244 (31.461)24,282 (31.511)Unknown sex22 (0.029)15 (0.019)Not Hispanic or Latino50,424 (65.435)50,470 (65.494)Unknown ethnicity22,734 (29.502)22,710 (29.471)Hispanic or Latino3902 (5.064)3880 (5.035)White51,144 (66.369)51,156 (66.385)Unknown race14,375 (18.654)14,380 (18.661)Black or African American8996 (11.674)8995 (11.673)Asian2259 (2.931)2271 (2.947)American Indian or Alaska Native22 (0.288)197 (0.256)Native Hawaiian or other Pacific Islander64 (0.083)61 (0.079)SD, Standard deviation. Open table in a new tab Table IIOdds ratios for diagnosis of select autoimmune conditions in lichen planus compared to control cohort, following lichen planus diagnosis (index event)ICD-10 codeOdds ratio95% Confidence intervalP valueConditions with increased odds Lichen sclerosusL90.04.0173.698-4.364<.0001 MorpheaL94.03.6303.217-4.095<.0001 Other local lupus erythematosusL93.22.3381.975-2.767<.0001 Subacute cutaneous lupus erythematosusL93.12.2671.717-2.992<.0001 Discoid lupus erythematosusL93.01.8761.677-2.097<.0001 Systemic lupus erythematosusM321.4751.346-1.616<.0001 Systemic sclerosisM341.4651.245-1.725<.0001 DermatomyositisM33.11.4501.067-1.971.0170 Sjogren's syndromeM35.01.3701.271-1.475<.0001 Primary biliary cirrhosisK74.31.3621.088-1.704.0067 Alopecia areataL631.3491.197-1.520<.0001 VitiligoL801.2181.087-1.364.0007 Autoimmune thyroiditisE06.31.1411.055-1.234.0010Conditions with decreased odds Vitamin D deficiencyE550.7770.757-0.798<.0001 Multiple sclerosisG350.7800.689-0.884<.0001 Type 1 diabetes mellitusE10.90.8290.759-0.906<.0001 PsoriasisL400.8690.832-0.907<.0001 Rheumatoid arthritisM06.90.9370.881-0.997.0408 Inflammatory arthritisM060.9380.887-0.992.0254Conditions with no association Reactive arthritisM02.91.2000.605-2.381.6015 Celiac diseaseK90.01.1150.992-1.253.0689 Psoriatic arthritisL40.51.0800.961-1.214.1990 Crohn's diseaseK501.0310.930-1.143.5634 Ulcerative colitisK511.0170.924-1.119.7332 Myasthenia gravisG700.9980.890-1.120.9766ICD-10, International Classification of Diseases-10. Open table in a new tab SD, Standard deviation. ICD-10, International Classification of Diseases-10. This study identified novel associations of LP with discoid lupus erythematosus, LS, morphea, other local lupus erythematosus, primary biliary cirrhosis, subacute cutaneous lupus erythematosus, systemic sclerosis, and vitiligo. Previously found associations were confirmed except for those with type 1 diabetes mellitus, inflammatory bowel disease, and celiac disease. Prior studies have reported an association between AD and autoimmune disease (inflammatory bowel disease, celiac disease, rheumatoid arthritis).5Ivert L.U. Wahlgren C.F. Lindelöf B. Dal H. Bradley M. Johansson E.K. Association between atopic dermatitis and autoimmune diseases: a population-based case-control study.Br J Dermatol. 2021; 185: 335-342Crossref PubMed Scopus (23) Google Scholar It is possible we underestimated associations by utilizing AD as a control. Further investigation is necessary to understand why LP patients have decreased odds of several autoimmune conditions. Study limitations include a retrospective design, possible misclassification in ICD-10 diagnoses, a single control group design, a US-only cohort, and inclusion of all LP forms (cutaneous, oral, genital) which may have different comorbidities. Additionally, while LP/LS and LP/cutaneous lupus overlap syndromes exist, it is possible that LS and cutaneous lupus were misdiagnosed as LP initially, due to overlapping clinical and histological features. Overall, these findings suggest LP is not an isolated skin disease, and patients with LP may be diagnosed with additional autoimmune conditions in the future. Such awareness may lead to earlier diagnosis of concomitant conditions and allow for the selection of medical therapies with overlapping therapeutic potential. None disclosed.